Cell and Tumor Biology Laboratory, North Eastern Hill University, Shillong-793022, India.
Anticancer Agents Med Chem. 2013 Sep;13(7):1096-114. doi: 10.2174/18715206113139990131.
The present work describes the anticancer activity of cantharidin isolated from red-headed blister beetles, Epicauta hirticornis and its possible mode of action involving induction of apoptosis, oxidative stress and decrease in glutathione against murine ascites Dalton's lymphoma. The structure of isolated compound was confirmed as cantharidin by X-ray diffraction method. Cantharidin treatment showed potent anticancer activity with an increase in life span (~ 87%) of tumor-bearing mice. Cantharidin treatment induced apoptosis in Dalton's lymphoma cells and also caused an oxidative stress due to generation of reactive oxygen species (ROS) and an increase in lipid peroxidation. The observed canthardin-mediated decrease in glutathione and glutathione related enzymes activities in the tumor cells may weaken the cellular antioxidant system. Moreover, cantharidin treatment also caused a significant decrease in mitochondrial cytochrome c and simultaneous increase in cytosolic cytochrome c which ultimately facilitates activation of caspase 9 and 3 to augment mitochondrial apoptotic pathway causing cancer cell death. Based on the present findings, it may be suggested that cantharidin-mediated anticancer activity could be due to decrease in the protective ability of cancer cells by ROS and subsequent activation of effecter caspases leading to apoptotic cell death.
本工作描述了从红头芫菁（Epicauta hirticornis）中分离出的斑蝥素的抗癌活性，以及其可能的作用模式，包括诱导细胞凋亡、氧化应激和降低谷胱甘肽水平，从而抑制小鼠腹水型 Dalton 淋巴瘤。通过 X 射线衍射法确定分离出的化合物的结构为斑蝥素。斑蝥素处理表现出很强的抗癌活性，可使荷瘤小鼠的寿命延长（~87%）。斑蝥素处理诱导 Dalton 淋巴瘤细胞凋亡，并由于活性氧（ROS）的产生和脂质过氧化增加而引起氧化应激。观察到的斑蝥素介导的肿瘤细胞中谷胱甘肽和谷胱甘肽相关酶活性的降低可能削弱了细胞抗氧化系统。此外，斑蝥素处理还导致线粒体细胞色素 c 显著减少，同时细胞质细胞色素 c 增加，这最终促进了半胱天冬酶 9 和 3 的激活，增强了线粒体凋亡途径，导致癌细胞死亡。基于目前的研究结果，可以认为，斑蝥素介导的抗癌活性可能是由于 ROS 降低了癌细胞的保护能力，随后激活效应半胱天冬酶导致细胞凋亡。
